Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Study information

Scientific title

Efficacy of primaquine against Plasmodium vivax relapses when combined with dihydroartemisinin-piperaquine or quinine in Indonesian soldiers

Acronym

Study hypothesis

The study aims to characterize the safety, tolerability, efficacy and pharmacokinetics of dihydroartemisinin-piperaquine (DHA-PQP) for the radical cure of P. vivax when combined with 14 days of primaquine

Study design

Primary study design

Secondary study design

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Malaria

Intervention

A single center randomized open label non-inferiority study of PQ treatment against the cumulative relapse rate over 1 year when administered with two different companion blood schizontocides as radical cure of vivax malaria. Enrolled subjects were randomly assigned to one of the following arms:

2. DHA-PP+PQ = combined dihydroartemsinin plus piperaquine (Euartesim™, Sigma Tau, Italy; DHA-PP; 40mg dihydroartemisinin base and 320mg of piperaquine base per tablet) of three tablets for participants < 75kg, or four tablet for participants > 75kg for three days, followed by 0.5mg/kg primaquine daily for 14 days commencing on day 28 after enrollment (no safety data guided co-administration of primaquine with DHA-PP)

3. AS alone = artesunate alone (Arsuamoon™, tablet of 50mg artesunate packaged with tablet of 196mg amodiaquine hydrochloride; Guilin Pharmaceuticals Co. Ltd, Shanghai, China) was administered in a total dose of 200mg on day of enrollment, followed by a single daily dose for 6 more days

Follow up was for 365 days, counting the first day of study drug administration as Day 0.

Intervention type

Drug

Phase

Not Applicable

Drug names

Dihydroartemisinin-piperaquine, quinine

Primary outcome measures

Measure and compare, using a non-inferior design, the cumulative relapse rate over one year of the two arms relative to the natural relapse rate

Secondary outcome measures

Measure the efficacy of the two primaquine combination regimens against relapse, relative to the relapse rate of the artesunate alone regimen.

Overall trial start date

01/11/2010

Overall trial end date

10/04/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male patients between the age of 18 and 60 years2. Traveled for >1 month to north eastern Papua within the past 12 months3. Body weight > 40 kg and ≤ 90 kg 4. Presence of P. vivax parasitemia mono- or mixed infection with another plasmodial species confirmed by positive microscopy of P. vivax with parasite density ≥20/ µL of blood 5. Written informed consent provided by patient. If the patient was unable to write, witnessed consent was permitted6. Glucose-6-phosphate dehydrogenase (G6PD) normal using the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) qualitative fluorescent spot test (Trinity Biologicals, USA) 7. Able to swallow oral medication8. Able and willing to participate based on information given to patient

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

80 participants per arm, total 240 participants.

Participant exclusion criteria

1. Presence of clinical condition requiring hospitalization2. Presence of significant anaemia, as defined by Hb < 8 g/dL3. G6PD deficient determined by a standard qualitative test 4. Definite plans for an absence of 3 days or more from the base within 28 days of being enrolled5. Known history or evidence of clinically significant disorders: 5.1. Cardiovascular5.2. A corrected QT interval (QTc) >450 ms* 5.3. Respiratory, including active tuberculosis5.4. Hepatic5.5. Renal5.6. Gastrointestinal5.7. Immunological5.8. Neurological, including hearing impairment5.9. Endocrine5.10. Infectious5.11. Malignancy5.12. Psychiatric6. Recent head trauma7. Any other clinically significant finding that the investigator judges will place the patient at risk or interfere with the study results8. Known to have or be confirmed:8.1. Active Hepatitis A (e.g. by detection of anti HAV-IgM)8.2. Hepatitis B surface antigen (HBsAg) carrier8.3. Hepatitis C antibody (HCV Ab).9. Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range 10. Renal impairment as indicated by abnormal creatinine clearance of < 60 ml/min, measured using Cockcroft-Gault formula11. Known history of hypersensitivity, allergy or adverse reactions to piperaquine, quinine or primaquine, artesunate, dihydroartemisinin (DHA) or other artemisinins12. Previous participation in the present clinical trial with DHA/PQP 13. Had received any investigational drug within the past 4 weeks